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. 2000 Feb;82(4):806–811. doi: 10.1054/bjoc.1999.1003

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

J W G van Putten 1, P Eppinga 3, Z Erjavec 4, G de Leede 5, J Nabers 6, J B E Smeets 7, D Th Sleijfer 2, H J M Groen 1
PMCID: PMC2374380  PMID: 10732750

Abstract

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaign

Keywords: non-small-cell lung cancer, chemotherapy, epirubicin, gemcitabine

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Selected References

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  1. Abratt R. P., Bezwoda W. R., Falkson G., Goedhals L., Hacking D., Rugg T. A. Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study. J Clin Oncol. 1994 Aug;12(8):1535–1540. doi: 10.1200/JCO.1994.12.8.1535. [DOI] [PubMed] [Google Scholar]
  2. Abratt R. P., Bezwoda W. R., Goedhals L., Hacking D. J. Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer. J Clin Oncol. 1997 Feb;15(2):744–749. doi: 10.1200/JCO.1997.15.2.744. [DOI] [PubMed] [Google Scholar]
  3. Antón A., Díaz-Fernández N., González Larriba J. L., Vadell C., Masutti B., Montalar J., Barneto I., Artal A., Rosell R. Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC). Lung Cancer. 1998 Nov;22(2):139–148. doi: 10.1016/s0169-5002(98)00069-5. [DOI] [PubMed] [Google Scholar]
  4. Bakker M., Groen H. J., Smit E. F., Smeets J., Riggi M., Postmus P. E. Phase I study of high-dose epirubicin and vinorelbine in previously untreated non-small-cell lung cancer stage IIIB-IV. Br J Cancer. 1995 Dec;72(6):1547–1550. doi: 10.1038/bjc.1995.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brocato N., Bruno M. F., Araujo C. E., Cervellino J. C., Pirisi C., Temperley G., Sparrow C., Savulsky C., Balbiani L. R. Treatment of non-small cell lung cancer with ifosfamide (IFO)+ 4'-epiadriamycin (EPI)+platinum vs. IFO+EPI: a GETLAC Study. Grupo de Estudio y Tratamiento Latinoamericano del Cáncer Study. Oncology. 1995 Jan-Feb;52(1):24–31. doi: 10.1159/000227422. [DOI] [PubMed] [Google Scholar]
  6. Bunn P. A., Jr Review of therapeutic trials of carboplatin in lung cancer. Semin Oncol. 1989 Apr;16(2 Suppl 5):27–33. [PubMed] [Google Scholar]
  7. Canellos G. P. Current strategies for early Hodgkin's disease. Ann Oncol. 1996;7 (Suppl 4):91–93. doi: 10.1093/annonc/7.suppl_4.s91. [DOI] [PubMed] [Google Scholar]
  8. Cardenal F., López-Cabrerizo M. P., Antón A., Alberola V., Massuti B., Carrato A., Barneto I., Lomas M., García M., Lianes P. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12–18. doi: 10.1200/JCO.1999.17.1.12. [DOI] [PubMed] [Google Scholar]
  9. Crinò L., Scagliotti G., Marangolo M., Figoli F., Clerici M., De Marinis F., Salvati F., Cruciani G., Dogliotti L., Pucci F. Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol. 1997 Jan;15(1):297–303. doi: 10.1200/JCO.1997.15.1.297. [DOI] [PubMed] [Google Scholar]
  10. Feld R., Wierzbicki R., Walde P. L., Shepherd F. A., Evans W. K., Gupta S., Shannon P., Lassus M. Phase I-II study of high-dose epirubicin in advanced non-small-cell lung cancer. J Clin Oncol. 1992 Feb;10(2):297–303. doi: 10.1200/JCO.1992.10.2.297. [DOI] [PubMed] [Google Scholar]
  11. Gatzemeier U., Shepherd F. A., Le Chevalier T., Weynants P., Cottier B., Groen H. J., Rosso R., Mattson K., Cortes-Funes H., Tonato M. Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study. Eur J Cancer. 1996 Feb;32A(2):243–248. doi: 10.1016/0959-8049(95)00444-0. [DOI] [PubMed] [Google Scholar]
  12. Georgoulias V., Kouroussis C., Androulakis N., Kakolyris S., Dimopoulos M. A., Papadakis E., Bouros D., Apostolopoulou F., Papadimitriou C., Agelidou A. Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial. J Clin Oncol. 1999 Mar;17(3):914–920. doi: 10.1200/JCO.1999.17.3.914. [DOI] [PubMed] [Google Scholar]
  13. Grant S. C., Gralla R. J., Kris M. G., Orazem J., Kitsis E. A. Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients. J Clin Oncol. 1992 Mar;10(3):484–498. doi: 10.1200/JCO.1992.10.3.484. [DOI] [PubMed] [Google Scholar]
  14. Launchbury A. P., Habboubi N. Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treat Rev. 1993 Jul;19(3):197–228. doi: 10.1016/0305-7372(93)90036-q. [DOI] [PubMed] [Google Scholar]
  15. Lilenbaum R. C., Langenberg P., Dickersin K. Single agent versus combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: a meta-analysis of response, toxicity, and survival. Cancer. 1998 Jan 1;82(1):116–126. doi: 10.1002/(sici)1097-0142(19980101)82:1<116::aid-cncr14>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  16. Marino P., Pampallona S., Preatoni A., Cantoni A., Invernizzi F. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994 Sep;106(3):861–865. doi: 10.1378/chest.106.3.861. [DOI] [PubMed] [Google Scholar]
  17. Plosker G. L., Faulds D. Epirubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy. Drugs. 1993 May;45(5):788–856. doi: 10.2165/00003495-199345050-00011. [DOI] [PubMed] [Google Scholar]
  18. Smit E. F., Berendsen H. H., Piers D. A., Smeets J., Riva A., Postmus P. E. A phase II study of high dose epirubicin in unresectable non small cell lung cancer. Br J Cancer. 1992 Mar;65(3):405–408. doi: 10.1038/bjc.1992.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Souquet P. J., Chauvin F., Boissel J. P., Cellerino R., Cormier Y., Ganz P. A., Kaasa S., Pater J. L., Quoix E., Rapp E. Polychemotherapy in advanced non small cell lung cancer: a meta-analysis. Lancet. 1993 Jul 3;342(8862):19–21. doi: 10.1016/0140-6736(93)91882-m. [DOI] [PubMed] [Google Scholar]
  20. Wilkes J. D. Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol. 1998 Oct;25(5):538–551. [PubMed] [Google Scholar]
  21. Wils J., Utama I., Sala L., Smeets J., Riva A. Phase II study of high-dose epirubicin in non-small cell lung cancer. Eur J Cancer. 1990;26(11-12):1140–1141. doi: 10.1016/0277-5379(90)90271-t. [DOI] [PubMed] [Google Scholar]

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